Gut microbiota, tight junction protein expression, intestinal resistance, bacterial translocation and mortality following cholestasis depend on the genetic background of the host
Open accessAbstract
Failure of the intestinal barrier is a characteristic feature of cholestasis. We have previously observed higher mortality in C57BL/6J compared with A/J mice following common bile duct ligation (CBDL). We hypothesized the alteration in gut barrier function following cholestasis would vary by genetic background. Following one week of CBDL, jejunal TEER was significantly reduced in each ligated mouse compared with their sham counterparts; moreover, jejunal TEER was significantly lower in both sham and ligated C57BL/6J compared with sham and ligated A/J mice, respectively. Bacterial translocation to mesenteric lymph nodes was significantly increased in C57BL/6J mice vs. A/J mice. Four of 15 C57BL/6J mice were bacteremic; whereas, none of the 17 A/J mice were. Jejunal IFN-γ mRNA expression was significantly elevated in C57BL/6J compared with A/J mice. Western blot analysis demonstrated a significant decrease in occludin protein expression in C57BL/6J compared with A/J mice following both sham operation and CBDL. Only C57BL/6J mice demonstrated a marked decrease in ZO-1 protein expression following CBDL compared with shams. Pyrosequencing of the 16S rRNA gene in fecal samples showed a dysbiosis only in C57BL/6J mice following CBDL when compared with shams. This study provides evidence of strain differences in gut microbiota, tight junction protein expression, intestinal resistance and bacterial translocation which supports the notion of a genetic predisposition to exaggerated injury following cholestasis.
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The gut microbiota can fine-tune the level of intestinal permeability by altering expression levels of tight junction proteins along the epithelial wall.
“By altering expression levels of tight junction proteins along the epithelial wall, and thus the level of bacterial infiltration in the mucosal layer, the gut microbiota can fine-tune the level of intestinal permeability (Karczewski et al., 2010; Alaish et al., 2013).”
From Microbiome–microglia connections via the gut–brain axis (2019) · cites this paper as Alaish et al., 2013
There are very limited available studies focused on characterising the microbiome composition during experimental cholestasis and these studies have shown conflicting results.
“Moreover, there are very limited available studies focused on characterising the microbiome composition during experimental cholestasis and these studies have shown conflicting results25,26.”
From Cholestasis induced by bile duct ligation promotes changes in the intestinal microbiome in mice (2019) · cites this paper as [25]
Alaish et al. described changes in Bl6/C57 mice at late stages after BDL (14 days) that the authors discussed to be associated with advanced fibrogenesis (cirrhosis).
“While Fouts et al.26 described that BDL did not alter the microbiome in mice, Alaish et al.25 described changes in Bl6/C57 mice at late stages after BDL (14 days) that the authors discussed to be associated with advanced fibrogenesis (cirrhosis).”
From Cholestasis induced by bile duct ligation promotes changes in the intestinal microbiome in mice (2019) · cites this paper as [25]
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References 60 · Cited by 54
- Authors
- Alaish, S. M., Smith, A. D., Timmons, J., Greenspon, J., Eyvazzadeh, D., Murphy, E., Shea-Donahue, T., Cirimotich, S., Mongodin, E., Zhao, A., Fasano, A., Nataro, J. P., & Cross, A. S.
- Affiliations
- University of Maryland, Baltimore (US)
- University of Virginia (US)
- Corresponding author
- Alaish, Samuel M.
- ORCID
- Venue
- Gut Microbes
- Publisher
- Informa UK Limited
- Published
- 2013-07-12
- Volume
- 4
- Issue
- 4
- Pages
- 292-305
- ISSN
- 1949-0976 (ISSN-L)
- 1949-0984
- PMC
- PMC3744514
- OpenAlex
- W1997434261
- Cited by
- 54
- References
- 60
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 7 · 2023: 8 · 2022: 5 · 2021: 2 · 2020: 7 · 2019: 2 · 2018: 4 · 2017: 6 · 2016: 3 · 2015: 2 · 2014: 1 · 2013: 1
- FWCI
- 1.05
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Gut Microbes (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of General Medical Sciences (K08GM081701)
- National Institute of Diabetes and Digestive and Kidney Diseases (T32DK067872)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- cholestasis, gut microbiota, intestinal barrier, tight junction proteins, occludin, ZO-1, bacterial translocation, common bile duct ligation, genetic background, C57BL/6J mice, A/J mice, intestinal epithelial permeability, interferon-gamma, dysbiosis, mortality, strain differences
- MeSH terms
- Animals, Cholestasis, Male, Mice, Inbred A, Mice, Inbred C57BL, Bacteremia, Bacterial Translocation, Genetic Predisposition to Disease, Gastrointestinal Tract, Mice, Tight Junction Proteins
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